Digital Commons Network^™

Bovine Lactoferrin For The Prevention Of Covid-19 Infection In Health Care Personnel: A Double-Blinded Randomized Clinical Trial (Lf-Covid), Rafaella Navarro, Jose Luis Paredes, Lourdes Tucto, Carlos Medina, Eddie Angles-Yanqui, Juan Carlos Nario, Jorge Ruiz-Cabrejos, Juan Luis Quintana, Kevin Turpo-Espinoza, Fernando Mejia-Cordero, Meylin Aphang-Lam, Jorge Florez, Gabriel Carrasco-Escobar, Theresa Jean Ochoa

Faculty, Staff and Student Publications

Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on suspected episodes. A serological test was obtained from all participants …

The Effects Of Gender And Country Of Origin On Acculturation, Psychological Factors, Lifestyle Factors, And Diabetes-Related Physiological Outcomes Among Mexican Americans: The Starr County Diabetes Prevention Initiative, Sharon A Brown, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, Mary A Winter, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

OBJECTIVES: Examine acculturation and psychological, lifestyle, and physiological factors based on gender and country of origin (U.S. vs. Mexico).

METHODS: Baseline data from the Starr County diabetes prevention study (

RESULTS: Participants were: predominantly female (73%); 51 years of age, on average; born in Mexico (71%); and Spanish-speaking. Individuals spent 11 of their waking hours (range = 0-18 h) in sedentary activities. Compared to females, more males spoke English and reported fewer hours in sedentary activities. Compared to participants born in Mexico, those born in the U.S. were more likely to: speak English; report depressive symptoms; and exhibit elevated BMI …

Stool-Based Tests Mitigate Impacts Of Covid-19 On Colorectal Cancer Screening, Po-Hong Liu, Amit G Singal, Caitlin C Murphy

Faculty, Staff and Student Publications

No abstract provided.

Beta-Blocker Use Is Associated With Worse Relapse-Free Survival In Patients With Head And Neck Cancer, Hannah Y Chen, Weilu Zhao, Shorook Na'ara, Frederico O Gleber-Netto, Tongxin Xie, Shahrukh Ali, Zachary M Thompson, Jane Buell, Haleigh Stafford, Priyadharsini Nagarajan, Michael Davies, Michael K Wong, Michael R Migden, Padmanee Sharma, Jeffrey N Myers, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

PURPOSE: Although beta-blockers (BBs) have been hypothesized to exert a beneficial effect on cancer survival through inhibition of beta-adrenergic signaling pathways, clinical data on this issue have been inconsistent. We investigated the impact of BBs on survival outcomes and efficacy of immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC), non-small-cell lung cancer (NSCLC), melanoma, or squamous cell carcinoma of the skin (skin SCC), independent of comorbidity status or cancer treatment regimen.

METHODS: Patients (N = 4,192) younger than 65 years with HNSCC, NSCLC, melanoma, or skin SCC treated at MD Anderson Cancer Center from 2010 to 2021 …

Survival Of Middle Eastern And North African Individuals Diagnosed With Colorectal Cancer: A Population-Based Study In California, Timothy A Zaki, Argyrios Ziogas, Jenny Chang, Caitlin C Murphy, Hoda Anton-Culver

Faculty, Staff and Student Publications

BACKGROUND: Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer-specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California.

METHODS: We identified adults (ages 18-79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer-specific survival and used Cox proportional hazards regression models to examine the association of …

Aligning Germline Cancer Predisposition With Tumor-Based Next-Generation Sequencing For Modern Oncology Diagnosis, Interception, And Therapeutic Development, Timothy A Yap, Zsofia K Stadler, Leigh Anne Stout, Bryan P Schneider

Faculty, Staff and Student Publications

In the era of precision medicine, genomic interrogation for identification of both germline and somatic genetic alterations has become increasingly important. While such germline testing was usually undertaken via a phenotype-driven single-gene approach, with the advent of next-generation sequencing (NGS) technologies, the widespread utilization of multigene panels, often agnostic of cancer phenotype, has become a commonplace in many different cancer types. At the same time, somatic tumor testing in oncology performed for the purpose of guiding therapeutic decisions for targeted therapies has also rapidly expanded, recently starting to incorporate not just patients with recurrent or metastatic cancer but even patients …

Cross-Sectional Association Between Neighborhood Socioeconomic Status And Sleep Duration Among Black And White Men And Women: The Southern Community Cohort Study, Samuel H Nyarko, Liying Luo, David G Schlundt, Qian Xiao

Faculty, Staff and Student Publications

Objective: To examine the association of neighborhood socioeconomic status (SES) with sleep duration among a large cohort of Black and white men and women in the United States.

Methods: We used data from the Southern Community Cohort Study (SCCS, N = 75,248). Neighborhood SES was based on census data and sleep duration was measured by self-report. Multinomial logistic regression analysis was performed to assess the association between neighborhood SES and short (<7 hours) and long (≥9 hours) sleep in the overall sample and according to race-sex subgroups.

Results: In the total sample, when compared with the highest quintile of neighborhood SES, the lowest quintile was associated with higher odds of both short (adjusted ORQ5 vs. …

Palliative Medicine Integration In The Usa: Cancer Centre Executives’ Attitudes, Joseph Chen, Allison De La Rosa, Dejian Lai, Rony Dev, Frances Lee Revere, David Lairson, Paige Wermuth, Eduardo Bruera, David Hui

Faculty, Staff and Student Publications

OBJECTIVES: To compare cancer centre (CC) executives' attitudes towards palliative care between National Cancer Institute-designated CCs (NCI-CCs) and non-NCI-designated CCs (non-NCI-CCs) in 2018 and to examine the changes in attitudes and beliefs between 2009 and 2018.

METHODS: CC chief executives at all NCI-CCs and a random sample of non-NCI-CCs were surveyed from April to August 2018. Twelve questions examined the executives' attitudes towards palliative care integration, perceived barriers and self-assessments. The primary outcome was agreement on the statement 'a stronger integration of palliative care services into oncology practice will benefit patients at my institution.' Survey findings from 2018 were compared …

Coffee Intake, Caffeine Metabolism Genotype, And Survival Among Men With Prostate Cancer, Justin R Gregg, Jeri Kim, Christopher Logothetis, Sam Hanash, Xiaotao Zhang, Ganiraju Manyam, Kenneth Muir, Graham G Giles, Janet L Stanford, Sonja I Berndt, Manolis Kogevinas, Hermann Brenner, Rosalind A Eeles, Practical Consortium, Peng Wei, Carrie R Daniel

Faculty, Staff and Student Publications

Background: Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized.

Objective: To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer.

Design, setting, and participants: Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163C>A rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and >6 mo of follow-up.

Outcome measurements and statistical analysis: Multivariable-adjusted Cox …

Dexmedetomidine Alters The Inflammatory Profile Of Rat Microglia In Vitro, Michael C Scott, Candice M Haase, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

BACKGROUND: Microglia are a primary mediator of the neuroinflammatory response to neurologic injury, such as that in traumatic brain injury. Their response includes changes to their cytokine expression, metabolic profile, and immunophenotype. Dexmedetomidine (DEX) is an α

METHODS: Primary microglia were isolated from Sprague-Dawley rats and cultured. Microglia were activated using multiple mediators: lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (Poly I:C), and traumatic brain injury damage-associated molecular patterns (DAMP) from a rat that sustained a prior controlled cortical impact injury. After activation, cultures were treated with DEX. At the 24-h interval, the cell supernatant and cells were collected for the following studies: …

An Ecological Momentary Assessment Study To Examine Covariates And Effects Of Concurrent And Simultaneous Use Of Electronic Cigarettes And Marijuana Among College Students, Anne Buu, James J Yang, Tzung-Shiang Ou, Joon Kyung Nam, Ganghui Suh, Hsien-Chang Lin

Faculty, Staff and Student Publications

INTRODUCTION: The prevalence of concurrent and simultaneous use of e-cigarette and marijuana among college students is high. Yet, the literature was mainly based on cross-sectional surveys with emphasis on the smoking route. This is the first ecological momentary assessment (EMA) study that examined the vaping route of nicotine-marijuana co-use and the associated short-term psychological effects.

METHODS: This study recruited 686 college student e-cigarette users to participate in an on-line survey and 7-day EMA. Frequent marijuana users (247) - using marijuana weekly or daily - were compared with infrequent/non-users (439) on academic performance, e-cigarette use patterns, and dependence and respiratory symptoms. …

Author Correction: The Power Of Genetic Diversity In Genome-Wide Association Studies Of Lipids, Sarah E Graham, Shoa L Clarke, Kuan-Han H Wu, Stavroula Kanoni, Greg J M Zajac, Shweta Ramdas, Ida Surakka, Ioanna Ntalla, Sailaja Vedantam, Thomas W Winkler, Adam E Locke, Eirini Marouli, Mi Yeong Hwang, Sohee Han, Akira Narita, Ananyo Choudhury, Amy R Bentley, Kenneth Ekoru, Anurag Verma, Bhavi Trivedi, Hilary C Martin, Karen A Hunt, Qin Hui, Derek Klarin, Xiang Zhu, Gudmar Thorleifsson, Anna Helgadottir, Daniel F Gudbjartsson, Hilma Holm, Isleifur Olafsson, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M Brumpton, Humaira Rasheed, Sanni E Ruotsalainen, Aki S Havulinna, Yogasudha Veturi, Qiping Feng, Elisabeth A Rosenthal, Todd Lingren, Jennifer Allen Pacheco, Sarah A Pendergrass, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E Miller, Archie Campbell, Kuang Lin, Iona Y Millwood, George Hindy, Asif Rasheed, Jessica D Faul, Wei Zhao, David R Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Anubha Mahajan, Michael R Brown, Weihua Zhang, Ketian Yu, Ellen M Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian'an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Gonneke Willemsen, Andrew R Wood, Yingji Ji, Zishan Gao, Simon Haworth, Ruth E Mitchell, Jin Fang Chai, Mette Aadahl, Jie Yao, Ani Manichaikul, Helen R Warren, Julia Ramirez, Jette Bork-Jensen, Line L Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Carlo Sidore, Edoardo Fiorillo, Aaron F Mcdaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T Møllehave, Betina H Thuesen, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E Galesloot, Jonathan P Bradfield, E Warwick Daw, Joseph M Zmuda, Jonathan S Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A Brody, Mary F Feitosa, Mary K Wojczynski, Michael Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W Benjamins, Jorgen Engmann, Rachel L Kember, Roderick C Slieker, Ken Sin Lo, Nuno R Zilhao, Phuong Le, Marcus E Kleber, Graciela E Delgado, Shaofeng Huo, Daisuke D Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Hampton L Leonard, Jonathan Marten, Börge Schmidt, Marina Arendt, Laura J Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Meraj Ahmed, Anne U Jackson, Noha A Yousri, Marguerite R Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R H J Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A Lange, Xiaoran Chai, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C Warner, Ya Xing Wang, Wen B Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Yi-Jen Hung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A Kentistou, Mathias Gorski, Marco Brumat, Karina Meidtner, Lawrence F Bielak, Jennifer A Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Chao Xue, Jifeng Zhang, Maria Pina Concas, Simona Vaccargiu, Peter J Van Der Most, Niina Pitkänen, Brian E Cade, Jiwon Lee, Sander W Van Der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Martina E Zimmermann, Jong Young Lee, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W Rayner, Carol A Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hildalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O Obura, Jessica Van Setten, Xiaoyin Li, Karen Schwander, Natalie Terzikhan, Jae Hun Shin, Rebecca D Jackson, Alexander P Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Heather M Highland, Kristin L Young, Takahisa Kawaguchi, Joachim Thiery, Joshua C Bis, Girish N Nadkarni, Lenore J Launer, Huaixing Li, Mike A Nalls, Olli T Raitakari, Sahoko Ichihara, Sarah H Wild, Christopher P Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Konain Fatima Bhatti, Dominique De Kleijn, Gert J De Borst, Eung Kweon Kim, Hieab H H Adams, M Arfan Ikram, Xiaofeng Zhu, Folkert W Asselbergs, Adriaan O Kraaijeveld, Joline W J Beulens, Xiao-Ou Shu, Loukianos S Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E Pennell, Trevor A Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M Heid, Klaus J Stark, Henry Völzke, Georg Homuth, Michele K Evans, Alan B Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E Hoefer, Susan Redline, Katja Pahkala, Albertine J Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Y Eugene Chen, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L R Kardia, Norihiro Kato, Matthias B Schulze, Giorgia Girotto, Bettina Jung, Carsten A Böger, Peter K Joshi, David A Bennett, Philip L De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J Caulfield, Patricia B Munroe, Xiuqing Guo, Marina Ciullo, Jost B Jonas, Nilesh J Samani, Jaakko Kaprio, Päivi Pajukanta, Linda S Adair, Sonny Augustin Bechayda, H Janaka De Silva, Ananda R Wickremasinghe, Ronald M Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke I Den Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G Wilson, Lars Lind, Chew-Kiat Heng, Amanda E Nelson, Yvonne M Golightly, James F Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J Scott, D C Rao, Donna K Arnett, Steven C Hunt, Mark Walker, Heikki A Koistinen, Giriraj R Chandak, Chittaranjan S Yajnik, Josep M Mercader, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, E Shyong Tai, Rob M Van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F Reilly, Amy Jayne Mcknight, Frank Kee, Karl-Heinz Jöckel, Mark I Mccarthy, Colin N A Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M Van Duijn, Fan Lu, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Esteban J Parra, Miguel Cruz, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M 'T Hart, Petra J M Elders, Scott M Damrauer, Meena Kumari, Mika Kivimaki, Pim Van Der Harst, Tim D Spector, Ruth J F Loos, Michael A Province, Bruce M Psaty, Ivan Brandslund, Peter P Pramstaller, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F A Grant, Lambertus A L M Kiemeney, Jacqueline De Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W Franks, Allan Linneberg, J Wouter Jukema, Amit V Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Francesco Cucca, Dennis O Mook-Kanamori, Ko Willems Van Dijk, Hugh Watkins, David P Strachan, Niels Grarup, Peter Sever, Neil Poulter, Jerome I Rotter, Thomas M Dantoft, Fredrik Karpe, Matt J Neville, Nicholas J Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T Hattersley, Nancy L Pedersen, Patrik K E Magnusson, Dorret I Boomsma, Eco J C De Geus, L Adrienne Cupples, Joyce B J Van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C Chambers, Jaspal S Kooner, Paul S De Vries, Alanna C Morrison, Kari E North, Martha Daviglus, Peter Kraft, Nicholas G Martin, John B Whitfield, Shahid Abbas, Danish Saleheen, Robin G Walters, Michael V Holmes, Corri Black, Blair H Smith, Anne E Justice, Aris Baras, Julie E Buring, Paul M Ridker, Daniel I Chasman, Charles Kooperberg, Wei-Qi Wei, Gail P Jarvik, Bahram Namjou, M Geoffrey Hayes, Marylyn D Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Unnur Thorsteinsdottir, Kari Stefansson, Yuk-Lam Ho, Julie A Lynch, Daniel J Rader, Philip S Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J O'Donnell, John M Gaziano, Peter Wilson, Charles N Rotimi, Scott Hazelhurst, Michèle Ramsay, Richard C Trembath, David A Van Heel, Gen Tamiya, Masayuki Yamamoto, Bong-Jo Kim, Karen L Mohlke, Timothy M Frayling, Joel N Hirschhorn, Sekar Kathiresan, Michael Boehnke, Pradeep Natarajan, Gina M Peloso, Christopher D Brown, Andrew P Morris, Themistocles L Assimes, Panos Deloukas, Yan V Sun, Cristen J Willer

Faculty, Staff and Student Publications

No abstract provided.

Persons Living With Dementia And Multiple Chronic Conditions Identifying Health Priorities With Care Partners, Thi Vu, Emily L Mroz, Kizzy Hernandez-Bigos, Denise Chow, Rafael Samper Ternent, Kalisha Bonds Johnson, Mary E Tinetti, Joan Monin

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of The Covid-19 Lockdown On Retinopathy Of Prematurity Screening And Management In The United States: A Multicenter Study, Shefali Sood, Mina M Naguib, David S Portney, Cagri G Besirli, Cole A Martin, C Armitage Harper, Maria P Fernandez, Audina M Berrocal, Polly A Quiram, Peter Belin, Noreen Clarke, Aaron Nagiel, Melissa Chandler, Christopher Bair, M Elizabeth Harnett, Vaidehi S Dedania

Faculty, Staff and Student Publications

Purpose: To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP).

Methods: In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020.

Results: A total of 1,645 patients met inclusion criteria. Among …

The Evidence Base For Surgical Treatment Of Infants With Necrotizing Enterocolitis Or Spontaneous Intestinal Perforation: Impact Of Trial Design And Questions Regarding Implementation Of Trial Recommendations, Parker T Evans, Martin L Blakely, Amanda S Mixon, Jennifer Canvasser, Matthew A Rysavy, Maria E Fernandez, Claudia Pedroza, Jon E Tyson

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Association Study And Functional Characterization Identifies Candidate Genes For Insulin-Stimulated Glucose Uptake, Alice Williamson, Dougall M Norris, Xianyong Yin, K Alaine Broadaway, Anne H Moxley, Swarooparani Vadlamudi, Emma P Wilson, Anne U Jackson, Vasudha Ahuja, Mette K Andersen, Zorayr Arzumanyan, Lori L Bonnycastle, Stefan R Bornstein, Maxi P Bretschneider, Thomas A Buchanan, Yi-Cheng Chang, Lee-Ming Chuang, Ren-Hua Chung, Tine D Clausen, Peter Damm, Graciela E Delgado, Vanessa D De Mello, Josée Dupuis, Om P Dwivedi, Michael R Erdos, Lilian Fernandes Silva, Timothy M Frayling, Christian Gieger, Mark O Goodarzi, Xiuqing Guo, Stefan Gustafsson, Liisa Hakaste, Ulf Hammar, Gad Hatem, Sandra Herrmann, Kurt Højlund, Katrin Horn, Willa A Hsueh, Yi-Jen Hung, Chii-Min Hwu, Anna Jonsson, Line L Kårhus, Marcus E Kleber, Peter Kovacs, Timo A Lakka, Marie Lauzon, I-Te Lee, Cecilia M Lindgren, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Jian'an Luan, Dina Mansour Aly, Elisabeth Mathiesen, Angela P Moissl, Andrew P Morris, Narisu Narisu, Nikolaos Perakakis, Annette Peters, Rashmi B Prasad, Roman N Rodionov, Kathryn Roll, Carsten F Rundsten, Chloé Sarnowski, Kai Savonen, Markus Scholz, Sapna Sharma, Sara E Stinson, Sufyan Suleman, Jingyi Tan, Kent D Taylor, Matti Uusitupa, Dorte Vistisen, Daniel R Witte, Romy Walther, Peitao Wu, Anny H Xiang, Björn Zethelius, Emma Ahlqvist, Richard N Bergman, Yii-Der Ida Chen, Francis S Collins, Tove Fall, Jose C Florez, Andreas Fritsche, Harald Grallert, Leif Groop, Torben Hansen, Heikki A Koistinen, Pirjo Komulainen, Markku Laakso, Lars Lind, Markus Loeffler, Winfried März, James B Meigs, Leslie J Raffel, Rainer Rauramaa, Jerome I Rotter, Peter E H Schwarz, Michael Stumvoll, Johan Sundström, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Robert Wagner, Inês Barroso, Mark Walker, Niels Grarup, Michael Boehnke, Nicholas J Wareham, Karen L Mohlke, Eleanor Wheeler, Stephen O'Rahilly, Daniel J Fazakerley, Claudia Langenberg

Faculty, Staff and Student Publications

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Overcoming The Challenges To Clinical Development Of X-Linked Retinitis Pigmentosa Therapies: Proceedings Of An Expert Panel, David G Birch, Janet K Cheetham, Stephen P Daiger, Carel Hoyng, Christine Kay, Ian M Macdonald, Mark E Pennesi, Lori S Sullivan

Faculty, Staff and Student Publications

X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease manifesting as impaired night vision and peripheral vision loss that progresses to legal blindness. Although several trials of ocular gene therapy for XLRP have been conducted or are in progress, there is currently no approved treatment. In July 2022, the Foundation Fighting Blindness convened an expert panel to examine relevant research and make recommendations for overcoming the challenges and capitalizing on the opportunities in conducting clinical trials of RPGR-targeted therapy for XLRP. Data presented concerned RPGR structure and mutation types known to cause XLRP, RPGR mutation-associated retinal phenotype diversity, patterns …

Leveraging A Surrogate Outcome To Improve Inference On A Partially Missing Target Outcome, Zachary R Mccaw, Sheila M Gaynor, Ryan Sun, Xihong Lin

Faculty, Staff and Student Publications

Sample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray) for leveraging information from a correlated surrogate outcome (eg, expression in blood) to improve inference on a partially missing target outcome (eg, expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Spray jointly models the …

Leucine-Rich Alpha-2-Glycoprotein 1 Is A Systemic Biomarker Of Early Brain Injury And Delayed Cerebral Ischemia After Subarachnoid Hemorrhage, Jude P J Savarraj, Devin W Mcbride, Eunsu Park, Sarah Hinds, Atzhiry Paz, Aaron Gusdon, Ren Xuefang, Sheng Pan, Hilda Ahnstedt, Gabriela Delevati Colpo, Eunhee Kim, Zhongming Zhao, Louise Mccullough, Huimahn Alex Choi

Faculty, Staff and Student Publications

BACKGROUND: After subarachnoid hemorrhage (SAH), early brain injury (EBI) and delayed cerebral ischemia (DCI) lead to poor outcomes. Discovery of biomarkers indicative of disease severity and predictive of DCI is important. We tested whether leucine-rich alpha-2-glycoprotein 1 (LRG1) is a marker of severity, DCI, and functional outcomes after SAH.

METHODS: We performed untargeted proteomics using mass spectrometry in plasma samples collected at < 48 h of SAH in two independent discovery cohorts (n = 27 and n = 45) and identified LRG1 as a biomarker for DCI. To validate our findings, we used enzyme-linked immunosorbent assay and confirmed this finding in an internal validation cohort of plasma from 72 study participants with SAH (22 DCI and 50 non-DCI). Further, we investigated the relationship between LRG1 and markers of EBI, DCI, and poor functional outcomes (quantified by the modified Rankin Scale). We also measured cerebrospinal fluid (CSF) levels of LRG1 and investigated its relationship to EBI, DCI, and clinical outcomes.

RESULTS: Untargeted proteomics revealed higher plasma LRG1 levels across EBI severity and DCI in both discovery cohorts. In the validation cohort, the levels of LRG1 were higher in the DCI group compared with the non-DCI group (mean (SD): …

Characterization Of The Cholesterol Biosynthetic Pathway In Dioscorea Transversa, Lauren J Salisbury, Stephen J Fletcher, Jeanette E Stok, Luke R Churchman, Joanne T Blanchfield, James J De Voss

Faculty, Staff and Student Publications

Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ^24,28 double bonds required for phytosterol biogenesis as well …

Oncolytic Dnx-2401 Virotherapy Plus Pembrolizumab In Recurrent Glioblastoma: A Phase 1/2 Trial, Farshad Nassiri, Vikas Patil, Leeor S Yefet, Olivia Singh, Jeff Liu, Rachel M A Dang, Takafumi N Yamaguchi, Mariza Daras, Timothy F Cloughesy, Howard Colman, Priya U Kumthekar, Clark C Chen, Robert Aiken, Morris D Groves, Shirley S Ong, Rohan Ramakrishna, Michael A Vogelbaum, Simon Khagi, Thomas Kaley, Jason M Melear, David M Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G Nair, Vinay K Puduvalli, Kenneth Aldape, Andrew Gao, Álvaro López-Janeiro, Carlos E De Andrea, Marta M Alonso, Paul Boutros, Joan Robbins, Warren P Mason, Adam M Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang, Gelareh Zadeh

Faculty, Staff and Student Publications

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response …

Sex- And Ethnic-Specific Patterns In The Incidence Of Hip Fracture Among Older Us Asian And Non-Hispanic White Adults, Joan C Lo, Malini Chandra, David R Lee, Jeanne A Darbinian, Nancy P Gordon, David W Zeltser, Christopher D Grimsrud, Catherine Lee

Faculty, Staff and Student Publications

BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences.

METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence …

Metabolic Adaptation To Consume Butyrate Under Prolonged Resource Exhaustion, Sophia Katz, Claudia Grajeda-Iglesias, Bella Agranovich, Alia Ghrayeb, Ifat Abramovich, Sabrin Hilau, Eyal Gottlieb, Ruth Hershberg

Faculty, Staff and Student Publications

Bacteria must often survive following the exhaustion of their external growth resources. Fitting with this need, many bacterial species that cannot sporulate, can enter a state known as long term stationary phase (LTSP) in which they can persist for years within spent media. Several recent studies have revealed the dynamics of genetic adaptation of Escherichia coli under LTSP. Yet, the metabolic consequences of such genetic adaptation were not addressed. Here, we characterized the metabolic changes LTSP populations experience, over the first 32 days under LTSP. This allowed us to link genetic adaptations observed in a convergent manner across LTSP populations …

Differential Effects Of An Ed-To-Home Care Transitions Intervention In An Older Adult Population: A Latent Class Analysis, Rebecca K Green, Kenneth J Nieser, Gwen C Jacobsohn, Amy L Cochran, Thomas V Caprio, Jeremy T Cushman, Amy J H Kind, Michael Lohmeier, Manish N Shah

Faculty, Staff and Student Publications

BACKGROUND: Older adults frequently return to the emergency department (ED) within 30 days of a visit. High-risk patients can differentially benefit from transitional care interventions. Latent class analysis (LCA) is a model-based method used to segment the population and test intervention effects by subgroup.

OBJECTIVES: We aimed to identify latent classes within an older adult population from a randomized controlled trial evaluating the effectiveness of an ED-to-home transitional care program and test whether class membership modified the intervention effect.

RESEARCH DESIGN: Participants were randomized to receive the Care Transitions Intervention or usual care. Study staff collected outcomes data through medical …

An End-To-End In-Silico And In-Vitro Drug Repurposing Pipeline For Glioblastoma, Ko-Hong Lin, Jay-Jiguang Zhu, Judith A Smith, Yejin Kim, Xiaoqian Jiang

Faculty, Staff and Student Publications

Our study aims to address the challenges in drug development for glioblastoma, a highly aggressive brain cancer with poor prognosis. We propose a computational framework that utilizes machine learning-based propensity score matching to estimate counterfactual treatment effects and predict synergistic effects of drug combinations. Through our in-silico analysis, we identified promising drug candidates and drug combinations that warrant further investigation. To validate these computational findings, we conducted in-vitro experiments on two GBM cell lines, U87 and T98G. The experimental results demonstrated that some of the identified drugs and drug combinations indeed exhibit strong suppressive effects on GBM cell growth. Our …

The Tgf-Β Superfamily As Potential Therapeutic Targets In Pancreatic Cancer, William A Grobman, Grecio J Sandoval, Torri D Metz, Tracy A Manuck, Rebecca G Clifton, Brenna L Hughes, George R Saade, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N Simhan, Dwight J Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L Bailit, Maged M Costantine, Harish M Sehdev, Alan T N Tita, George A Macones

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether preterm birth rates changed in relation to the onset of the coronavirus disease 2019 (COVID-19) pandemic and whether any change depended on socioeconomic status.

METHODS: This is an observational cohort study of pregnant individuals with a singleton gestation who delivered in the years 2019 and 2020 at 1 of 16 U.S. hospitals of the Maternal-Fetal Medicine Units Network. The frequency of preterm birth for those who delivered before the onset of the COVID-19 pandemic (ie, in 2019) was compared with that of those who delivered after its onset (ie, in 2020). Interaction analyses were performed for …

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Causal Linkage Of Presence Of Mutant Npm1 To Efficacy Of Novel Therapeutic Agents Against Aml Cells With Mutant Npm1, Christopher P Mill, Warren Fiskus, Kaberi Das, John A Davis, Christine E Birdwell, Tapan M Kadia, Courtney D Dinardo, Naval Daver, Koichi Takahashi, Koji Sasaki, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

In AML with NPM1 mutation causing cytoplasmic dislocation of NPM1, treatments with Menin inhibitor (MI) and standard AML chemotherapy yield complete remissions. However, the causal and mechanistic linkage of mtNPM1 to the efficacy of these agents has not been definitively established. Utilizing CRISPR-Cas9 editing to knockout (KO) or knock-in a copy of mtNPM1 in AML cells, present studies demonstrate that KO of mtNPM1 from AML cells abrogates sensitivity to MI, selinexor (exportin-1 inhibitor), and cytarabine. Conversely, the knock-in of a copy of mtNPM1 markedly sensitized AML cells to treatment with MI or cytarabine. Following AML therapy, most elderly patients with …

Dural Sinus Narrowing In Patients With Spontaneous Anterior Skull Base Cerebrospinal Fluid Leak, Karim W Asi, Brian H Cameron, Elliot R Friedman, Jeffrey P Radabaugh, Martin J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

OBJECTIVES: Current evidence suggests a link between idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (sCSF) leak, as well as between IIH and dural venous sinus (DVS) narrowing. However, there are limited data linking DVS narrowing and sCSF leak. This study aims to determine the prevalence of DVS narrowing in patients with sCSF leak.

METHODS: A retrospective review of all patients with sCSF leak that presented to a tertiary academic center from 2008 to 2019. Preoperative imaging was independently reviewed by two neuroradiologists to evaluate for DVS narrowing. Available literature was used to estimate the prevalence of DVS narrowing in …

National Institutes Of Health Diversity Supplement Awards: Experience Of Radiation Oncology Principal Investigators And Trainees, Afua A Yorke, Michael K Rooney, Jillian Rigert, Amy C Moreno, Clifton D Fuller, Eric C Ford

Faculty, Staff and Student Publications

No abstract provided.